Cardiorespiratory fitness, physical activity, and fatigue three months after first-ever ischemic stroke.

BACKGROUND: Research on cardiorespiratory fitness (CRF) in relation to physical activity (PA) and fatigue after stroke is limited. Increased knowledge of interrelationships between these factors can help optimize rehabilitation strategies and improve health-outcomes. OBJECTIVES: We aimed to: 1) evaluate CRF, PA, and fatigue, 2) characterize patients with impaired versus non-impaired CRF, and 3) examine associations of CRF with PA and fatigue, three months after first-ever ischemic stroke. METHODS: In this cross-sectional study CRF was measured as peak oxygen uptake (VO2peak) by cardiopulmonary exercise testing. PA was measured using accelerometers. Fatigue was assessed with the 7-item Fatigue Severity Scale (FSS). RESULTS: The sample (n=74, mean age 64±13 years, 36% women) had a mean VO2peak of 27.0±8.7 (86% of predicted). Fifty-one percent met the World Health Organization's recommendation of ≥150 min of moderate PA/week. Mean steps-per-day was 9316±4424 (113% of predicted). Thirty-five percent of the sample had moderate-to-high fatigue (FSS≥4), mean FSS score was 3.2±1.8.  Patients with impaired CRF (VO2peak<80% of predicted) had higher body-fat-percent (p<0.01), less moderate-to-vigorous PA (MVPA) (p<0.01) and a trend toward higher fatigue (p=0.053) compared to the non-impaired. Backward regression analysis showed that higher CRF was associated with more MVPA (unstandardized beta [95% CI]: 0.38 [0.15, 0.63], p=0.002) and less fatigue (unstandardized beta [95% CI]: -3.9 [-6.4, -1.6], p=0.004). CONCLUSIONS: Stroke patients had lower CRF compared to reference values. Impaired CRF was mainly related to overweight. Higher CRF was associated with more MVPA and less fatigue. Exercise after stroke may be especially beneficial for patients with impaired CRF.

Perioperative complications in cleft palate repair with Robin sequence following Tuebingen palatal plate treatment.

Our study aimed to evaluate perioperative complications following our institutional pre- and intraoperative management in cleft palate repair with Robin sequence (RS). RS patients who underwent cleft palate repair between 2000 and 2020 were retrospectively analysed. RS children with complete documentation and whose initial treatment involved the Tuebingen palatal plate (TPP) were included. Clinical records and operative charts were reviewed with regard to clinical characteristics as well as the neonatal and perioperative course. Results before and after adjustment of the anesthesiology protocol in 2014 were compared. 143 RS patients (41% male, 59% female) were included. Median pretherapeutic mixed-obstructive apnea index (MOAI) after birth was 9.4/hour (IQR 20.0). TPP treatment was associated with normalisation of the MOAI and adequate weight gain until surgery. At surgery, median age was 10 months (IQR 3), MOAI 0.1/h (IQR 0.5), and weight 8.7 kg (IQR 1.7). In 93% of cases (n = 133), the postoperative course was uneventful. Refinement of the anesthesiology protocol showed positive effects on the perioperative course and led to a reduction in perioperative events (10.7% vs. 2.9%). No severe perioperative complications occurred. We recommend the adoption of TPP treatment in the therapy of RS children. Our favourable results show that early TPP treatment minimizes perioperative complications in cleft palate repair by effectively and sustainably correcting upper airway obstruction.

Effects of guided deep breathing on breathlessness and the breathing pattern in chronic obstructive pulmonary disease: a double-blind randomized control study.

OBJECTIVE: To investigate whether guided deep breathing using a device improves breathlessness, quality of life, and breathing pattern in moderate and severe stage of chronic obstructive pulmonary disease (COPD). METHODS: In total, 150 patients participated in a double-blind randomized controlled trial in a four-week intervention and a four-month follow-up. Participants were randomized into a guided deep breathing group (GDBG), music listening group (MLG), or sitting still group (SSG). The patients' symptom score using the St George's Respiratory Questionnaire (SGRQ), and a Global Rating Change scale (GRC) was applied to measure breathlessness as primary outcome. The activity score and impact score of SRGQ, and breathing pattern were secondary outcomes. RESULTS: Positive effects of the GDBG were detected in GRC scale in breathlessness at four weeks (p=0.03) with remaining effect compared to MLG (p=0.04), but not to SSG at four months follow-up. GDBG showed positive effect for respiratory rate (p<0.001) at four weeks follow-up. A positive significant change (p<0.05-0.01) was found in all groups of SGRQ symptom score. CONCLUSION: GDBG had a beneficial effect on respiratory pattern and breathlessness. MLG and SSG also yielded significant improvements. PRACTICE IMPLICATIONS: Guided deep breathing may be used as a self-management procedure.

Massive monoclonal expansion of CD4 T-cells specific for a Mycobacterium tuberculosis ESAT-6 peptide.

T-cell responses towards tuberculin (purified protein derivative; PPD) or the Mycobacterium tuberculosis-specific antigens early secretory antigenic target (ESAT)-6 and culture filtrate protein-10 are indicative of prior contact with mycobacterial antigens. In this study, we investigated the exceptional case of a 75-yr-old patient who devoted more than one-third of his CD4 T-cells against PPD and ESAT-6. Antigen-specific T-cells were characterised using flow cytometric intracellular cytokine staining, ELISPOT assay, proliferation assays, and T-cell receptor spectratyping. T-cell frequencies were far above those found in age-matched controls (median 0.33%, range 0.05-6.32%) and remained at high levels for >2 yrs. The patient initially presented with haemoptysis, but active tuberculosis was ruled out by repeated analysis of sputum and bronchoalveolar lavage fluid. Skin testing was negative and haemoptyses did not have a M. tuberculosis-related aetiology. Phenotypical and functional properties of specific T-cells were consistent with a terminally differentiated effector-memory phenotype with capacity to produce interferon-γ, interleukin-2 and tumour necrosis factor-α. Epitope mapping showed that the CD4 T-cells were directed against a single peptide from ESAT-6 (amino acid 5-20) that was presented in context of HLA-DR. T-cell receptor Vß-spectratyping and sequencing of specific CD4 T-cells revealed a prominent peak fraction of monoclonal origin. In conclusion, similar to monoclonal gammopathies of undetermined significance, this may represent the first T-cell counterpart with known specificity against M. tuberculosis.

Whole-blood flow-cytometric analysis of antigen-specific CD4 T-cell cytokine profiles distinguishes active tuberculosis from non-active states.

T-cell based IFN-γ release assays do not permit distinction of active tuberculosis (TB) from successfully treated disease or latent M. tuberculosis infection. We postulated that IFN-γ and IL-2 cytokine profiles of antigen-specific T cells measured by flow-cytometry ex vivo might correlate with TB disease activity in vivo. Tuberculin (PPD), ESAT-6 and CFP-10 were used as stimuli to determine antigen-specific cytokine profiles in CD4 T cells from 24 patients with active TB and 28 patients with successfully treated TB using flow-cytometry. Moreover, 25 individuals with immunity consistent with latent M. tuberculosis infection and BCG-vaccination, respectively, were recruited. Although the frequency of cytokine secreting PPD reactive CD4 T cells was higher in patients with active TB compared to patients with treated TB (median 0.81% vs. 0.39% of CD4 T cells, p = 0.02), the overlap in frequencies precluded distinction between the groups on an individual basis. When assessing cytokine profiles, PPD specific CD4 T cells secreting both IFN-γ and IL-2 predominated in treated TB, latent infection and BCG-vaccination, whilst in active TB the cytokine profile was shifted towards cells secreting IFN-γ only (p<0.0001). Cytokine profiles of ESAT-6 or CFP-10 reactive CD4 T cells did not differ between the groups. Receiver operator characteristics (ROC) analysis revealed that frequencies of PPD specific IFN-γ/IL-2 dual-positive T cells below 56% were an accurate marker for active TB (specificity 100%, sensitivity 70%) enabling effective discrimination from non-active states. In conclusion, a frequency lower than 56% IFN-γ/IL-2 dual positive PPD-specific circulating CD4 T-cells is strongly indicative of active TB.

Comparison of 99mtechnetium-pertechnetate and 123iodide SPECT with FDG-PET in patients suspicious for breast cancer.

PURPOSE: Breast carcinomas express the Na(+)/I() symporter and may-albeit not a routine procedure-be imaged with (123)iodide ((123)I) and (99m)technetium-pertechnetate ((99m)TcO(4)(-)) scintigraphy. The aim of our prospective study was the comparison of (99m)TcO(4)(-)--and (123)I-single-photon emission computed tomography (SPECT) with (18)F-2-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) in patients suspicious for breast cancer. METHODS: Twenty-nine (29) untreated patients suspected of having breast carcinoma were prospectively examined with thorax SPECT with (99m)TcO(4)(-) (n=19) or (123)I (n=10), respectively, and FDG-PET (n=29) prior to biopsy. Tumor-to-background ratios (TBRs) were calculated for SPECT findings. Mean and maximum standardized uptake values (SUVs) were calculated for PET findings. Findings were compared in an intra-individual lesion-to-lesion analysis. RESULTS: In 28 of 29 patients, malignancy was verified with histopathology. In imaging the primary tumor, sensitivities of (99m)TcO(4)(-)-SPECT, (123)I-SPECT, and FDG-PET were 63%, 67%, and 89%, respectively. TBR maximum was 2.6+/-1.1 in (99m)TcO(4)()-SPECT and 2.3+/-0.6 in (123)I-SPECT. In FDG-PET, mean tumor SUV was 4.1+/-4 and maximum tumor SUV was 5.4+/-5.1. In contrast to FDG-PET, (99m)TcO(4)()-SPECT was ineffective in imaging nodal and distant metastases in the thorax, and (123)I-SPECT failed in imaging lymph node infiltrations. Distant metastases were not present in patients of the (123)I group, and the value of (123)I-SPECT was not evaluated. CONCLUSIONS: In contrast to FDG-PET, (99m)TcO(4)(-) and (123)I-SPECT are ineffective in imaging breast carcinoma in clinical practice.

Humoral immune responses of lung cancer patients against tumor antigen NY-ESO-1.

The cancer-associated antigen NY-ESO-1 is expressed in a number of malignancies of different histological type. Patients with NY-ESO-1 expressing tumors have been shown to bear circulating autoantibodies against this antigen. In this study, we have assessed the NY-ESO-I autoantibody response in patients with lung cancer by a serum ELISA. Using a serum dilution of 1:400 we detected seroreactivity in 35 of 175 (20%) of patients. Incidence of autoantibodies was significantly higher in patients suffering from non small cell lung cancer (NSCLC, 23%) as compared to those with small cell lung cancer (SCLC, 9%). In the NSCLC group, NY-ESO-I antibody was significantly more frequent in patients with undifferentiated tumors (40%) as compared to patients with either adenocarcinoma or squamous cell carcinoma (15 and 29%). Our observations indicate that induction of NY-ESO-I autoantibodies depends on the histological subtype within a given tumor entity.

CrELISA: a fast and robust enzyme-linked immunosorbent assay bypassing the need for purification of recombinant protein.

A multitude of antigens has been recently identified by screening of cDNA expression libraries derived from human tumors with autologous sera. Using a phage autoantibody assay and small panels of sera derived from cancer patients or controls it has been shown that some of these antigens display cancer-associated autoantibody responses. The diagnostic and prognostic significance of these potentially cancer-related autoantibodies remains unclear until large-scale assays are developed and serological data are available for hundreds of cancer patients and controls. The major bottleneck for the development of large-scale assays are the cloning, expression and the purification of each of the respective antigens. Due to these limitations and despite the potential clinical relevance large-scale autoantibody tests are established for only a few of these tumor antigens. Here we describe an enzyme-linked immunosorbent assay, Crude lysate ELISA (CrELISA), suitable for antigens identified by expression screening based on crude lysates of antigen-expressing bacteria. This assay permits sensitive and specific autoantibody seroscreening without the need of laborious and time-consuming cloning, expression and purification of recombinant proteins. CrELISA is robust and provides a versatile high throughput procedure for the rapid evaluation of multiple antigens in large-scale serology.

Tuberculin skin testing underestimates a high prevalence of latent tuberculosis infection in hemodialysis patients.

BACKGROUND: Identification of latent Mycobacterium tuberculosis infection in hemodialysis patients is hampered by reduced sensitivity of the established tuberculin skin test. We investigated whether in vitro quantitation of purified protein derivative (PPD)-specific T cells using a rapid 6-hour assay may represent an alternative approach for detecting latent infection. METHODS: One hundred and twenty-seven hemodialysis patients and 218 control patients (blood donors, health care workers, and control patients) were analyzed. Specific T cells toward PPD and early secretory antigenic target-6 (ESAT-6), a protein expressed in Mycobacterium tuberculosis but absent from M. bovis bacillus Calmette-Guerin (BCG) vaccine strains, were flow cytometrically quantified from whole blood, and results were compared with skin testing. RESULTS: Compared to blood donors, a high proportion of both health care workers (48.6%) and hemodialysis patients (53.5%) had PPD-specific Th1-type CD4 T-cell reactivity with similar median frequencies of PPD-specific T cells (0.17%; 0.06-3.75% vs. 0.26%; 0.06-4.12%, respectively). In contrast, skin test reactivity was significantly reduced in hemodialysis patients. Whereas 85.7% of control patients with PPD reactivity in vitro were skin test-positive, the respective percentage among hemodialysis patients was 51.4% (P= 0.007). Among individuals with PPD reactivity in vitro, approximately 50% had T cells specific for ESAT-6. CONCLUSION: Unlike the skin test, measurement of PPD reactivity by in vitro quantitation of PPD-specific T cells was unaffected by uremia-associated immunosuppression. This whole-blood assay may thus be a valuable alternative to skin testing, and detection of ESAT-6-specific T cells could moreover allow distinction of latent M. tuberculosis infection from BCG-induced reactivity to PPD. The assay is well suited for clinical use and may facilitate targeting of preventative therapy in high-risk individuals.